Kirk
Erickson, right, a psychology postdoctoral research
associate, is the lead author of a study that found
that women pondering hormone-replacement therapy should
consider regular exercise. Also pictured are co-author
Arthur F. Kramer, a Beckman researcher and psychology
professor, and Nancy Dodge, senior MRI technologist.

CHAMPAIGN, Ill.
— Women pondering hormone-replacement therapy also should consider
regular exercise. A new study at the University of Illinois at Urbana-Champaign
suggests that being physically fit offsets cognitive declines attributed
to long-term therapy.

“This study not only tells us that there is a benefit to being
highly fit, it pinpoints where in the brain it matters for postmenopausal
women who have been using the two strategies,” said lead author
Kirk I. Erickson, a postdoctoral researcher at the Beckman
Institute for Advanced Science and Technology at Illinois.

The study appeared online this month in advance of regular publication
in the journal Neurobiology of Aging. By using magnetic resonance imaging
and voxel-based morphometry (VBM), researchers documented the combined
effects on specific areas of the brain based on fitness of short- and
long-term users of hormone therapy.

Researchers also looked at how well 54 postmenopausal women performed
on a computerized version of the Wisconsin Card Sort Test, in which
constantly changing rules challenge memory, inhibition and task-switching
abilities known as executive functions. The women were divided into
groups based on use or non-use and duration of hormone therapy and existing
fitness levels.

“We found that higher fitness levels enhance the effects of shorter
durations of hormone treatment and offset the declines associated with
long-term use,” said Arthur F. Kramer, a Beckman researcher and psychology professor.
“It may be that a combination of HRT and exercise boosts both
cognition and brain structure of older women.”

Participants ranged in age from 58 to 80, with a mean age of 70. Hormone
status and duration of use were assessed based on their self-reports,
and aerobic fitness was measured by monitoring respiration, heart rate
and blood pressure during a treadmill test.

MRI images of the participants’ brains were taken, segmented into
3-D maps and analyzed by VBM, which allows for high spatial resolution
of the volume of gray and white matter. The women also were screened
for duration of hormone use, aerobic fitness levels, age, education,
socioeconomic status, age at menopause and for dementia.

VBM analysis revealed that four regions of gray matter – left
and right prefrontal cortex, left parahippocampal gyrus and left subgenual
cortex – varied with duration of hormone treatment. Longer hormone
usage resulted in significantly less tissue volume in these areas. However,
higher fitness scores were tied to greater tissue volume.

While there were no significant effects of the interaction of hormone
duration and fitness on white matter in general, higher fitness levels
were tied to greater prefrontal white matter regions and in the genu
of the corpus callosum, a key area that interconnects frontal areas
of the brain.

“Critically, the tissue volume measures in all four gray matter
regions revealed that high fitness levels were associated with a more
modest decline in regional brain volume than low fitness levels with
increasing durations of hormone therapy,” the researchers wrote.
“High fitness levels also were associated with a significant sparing
of the neural tissue of women not receiving hormone replacement therapy.

Durations of therapy of less than 10 years showed enhanced tissue volume
compared with all other groups, and the decline in tissue volume only
began after 11 to 15 years of hormone-replacement therapy.

Erickson and Kramer noted that their findings in women were in line
with previous animal studies that have found that estrogen and fitness
have similar mechanisms in the brain. Estrogen and fitness both stimulate
brain-derived neurotropic factor, a molecule tied to the production
of capillaries, plasticity and neurons.

These preliminary findings are based on only a small sampling of women
and need to be considered in a much broader clinical setting, Kramer
said. However, the findings mirror similar studies in his lab that are
continuing to show the benefits of physical fitness in older people.

Co-authors with Erickson and Kramer were Stanley J. Colcombe, a research
scientist at the Beckman Institute; Paige E. Scalf, a postdoctoral researcher
in Kramer’s lab; Edward McAuley, a Beckman researcher and professor
of kinesiology and psychology; McAuley’s former doctoral student Steriani Elavsky;
and Donna L. Korol, professor of psychology.

The research was funded by the National Institute on Aging and the Institute
for the Study of Aging.